P649: SAFETY AND EFFECTIVENESS IN NAIVE CLL PATIENTS TREATED WITH VEN AND OBI UNDER REAL-WORLD CONDITIONS - COMPARISON OF PATIENTS IN LINE OR OUT OF SCOPE WITH CLL14 TRIAL.
Authors: Schwaner Ingo, Holger Hebart, Christof Losem, Wolff Thomas, Schmidt Burkard, Rossi David, Lehmann Caroline, Benzel Julia, Huelsenbeck Johannes, Pichler Petra
Journal: HemaSphere (2023)

Background: Efficacy and safety of Venetoclax in combination with Obinutzumab (VenO) in treatment naive chronic lymphocytic leukaemia (CLL) patients was demonstrated in the CLL14 trial1. However, real-world data is limited, especially for patients who would not have been eligible for participation in CLL14, due to inclusion criteria. Aims: Effectiveness and safety data were analyzed for therapy naive patients treated with VenO. Patient data in line with CLL14 inclusion criteria2 versus out of scope of these trials were compared. Methods: VeRVe is a non-interventional, observational, prospective study with 60 study sites in Germany, Austria, and Switzerland. CLL patients treated with VenO according to the local label3 were subdivided based on main inclusion criteria of CLL14 (CIRS >6 and/ or creatinine clearance <70ml/min) into “eligible” and “ineligible” patients for descriptive analysis. Results: Until November 4th, 2022, 82 CLL patients were enrolled and received at least one dose of Ven. 39 (47.6%) of them were in the eligible and 43 (52.4%) ineligible group. The reasons for not fulfilling inclusion criteria were a CIRS score ≤6 and adequate renal function with a clearance ≥70 ml/min. For those patients eligible for CLL14, we noted that 15% had a CIRS score >6 and 32% a clearance <70 ml/min. The median duration of the ramp-up phase was 34 days in both groups. 23% of eligible patients and 11% of ineligible patients required therapy interruption (median 7 days). 84.6%/81.4% of the eligible/ineligible group had at least one comorbidity. TP53 mutation and/or del(17p) were present in 40.9% of eligible patients with available genetic data and 22.6% of ineligible patients with genetic information. Unmutated IGHV was detected in 60.9% of tested eligible patients and 66.7% of tested ineligible patients. Best overall response rate (ORR) within 12 months was 91.1% (48.5% CR/CRi and 42.6% PR) in total, 90.6% in the eligible and 91,6% in the ineligible group. With a median observation time of 9.5 months (range 0.1-20.6), estimated 12 months OS and PFS were identical with 95.8% in total population. Grade ≥3AEs/SAEs occurred in 36.6%/ 19.5% of patients in the total population. Summary/Conclusion: Patients who would have been ineligible for CLL14 were younger. The groups were comparable regarding comorbidities and differed, however, with respect to genetic risk factors. VenO led to high ORR and CR/CRi-rates in this population and was well tolerated, with slightly more grade ≥3 AEs and SAEs in the ineligible group. Overall, the VeRVe data are in line with previously reported CLL14 data1. Effectiveness of VenO therapy was comparable for eligible and ineligible patients, supporting the strong impact of VenO for a broad patient group in the treatment naive setting References [1] Al-Sawaf O et al., Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 5-year results of the randomized CLL 14 study. EHA 2022, S148 [2] Fischer K, et al., N Engl J Med 2019; 380:2225-36 [3] Venetoclax SmPC, October 2022 Keywords: Venetoclax, Chronic lymphocytic leukemia